GRAF is a multidomain protein that is necessary for the CLIC/GEEC endocytic pathway, the most prevalent clathrin-independent endocytic pathway discovered to date. By virtue of an N-terminal BAR domain, GRAF1 sculpts the endocytic membranes of this pathway into 40 nm diameter tubules and vesicles that allow uptake of extracellular fluid, GPI-linked proteins and certain bacterial exotoxins into cells. The role of dynamin in the CLIC/GEEC pathway is controversial, but GRAF1 interacts strongly with this protein and acute inhibition of dynamin action abrogates CLIC/GEEC endocytosis. There are several members of the GRAF family of proteins, including GRAF2, GRAF3, and oligophrenin, all of which likely playing similar roles during clathrin-independent endocytic events. Mutations of both GRAF1 and oligophrenin are strongly implicated in causing human disease (leukaemia and mental retardation, respectively).
^Shibata H, Oishi K, Yamagiwa A, Matsumoto M, Mukai H, Ono Y (2001). "PKNbeta interacts with the SH3 domains of Graf and a novel Graf related protein, Graf2, which are GTPase activating proteins for Rho family". J. Biochem.130 (1): 23–31. doi:10.1093/oxfordjournals.jbchem.a002958. PMID11432776.
Shibata H, Oishi K, Yamagiwa A, et al. (2001). "PKNbeta interacts with the SH3 domains of Graf and a novel Graf related protein, Graf2, which are GTPase activating proteins for Rho family". J. Biochem.130 (1): 23–31. doi:10.1093/oxfordjournals.jbchem.a002958. PMID11432776.
Taylor JM, Macklem MM, Parsons JT (1999). "Cytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho". J. Cell. Sci. 112 ( Pt 2): 231–42. PMID9858476.
Ishikawa K, Nagase T, Suyama M, et al. (1998). "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res.5 (3): 169–76. doi:10.1093/dnares/5.3.169. PMID9734811.
Billuart P, Bienvenu T, Ronce N, et al. (1998). "Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation". Nature392 (6679): 923–6. doi:10.1038/31940. PMID9582072.
Taylor JM, Hildebrand JD, Mack CP, et al. (1998). "Characterization of graf, the GTPase-activating protein for rho associated with focal adhesion kinase. Phosphorylation and possible regulation by mitogen-activated protein kinase". J. Biol. Chem.273 (14): 8063–70. doi:10.1074/jbc.273.14.8063. PMID9525907.